Traces of Anxiety Drug May Affect Fish Behavior, Study Shows

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Traces of a common psychiatric medication that winds up in rivers and streams may affect fish behavior and feeding patterns, according to a new study in the journal Science.

Researchers in Sweden exposed wild European perch to water with different concentrations of Oxazepam, a generic anti-anxiety medication that can show up in waterways after being flushed, excreted or discarded.

Researchers reported that fish exposed to Oxazepam became less social, more active and ate faster, behaviors they said could have long-term consequences for aquatic ecosystems.

Scientists who study pharmaceuticals in waterways said the research was intriguing because it examined the potential effect on animals of a specific medication designed to affect human behavior.

"It seems to be a solid study with an environmentally relevant species," said Donald Tillitt, an environmental toxicologist with the United States Geological Survey who was not involved in the study. He said it made sense that a medication that binds with a certain brain receptor in people could act similarly in fish, and the measures of behavior -- activity, sociability, boldness and feeding rate -- "are all important ones that we like to look at when we're trying to see the environmental effects of pharmaceuticals."

Still, because even the lowest concentration of Oxazepam in the study was higher than that found in the Swedish waterway researchers tested, "the relevance of their study to the real world is unclear," the Environmental Protection Agency said in written answers to questions.

The agency said that while "most pharmaceuticals do not seem to pose known risks to humans, animals or the rest of the ecosystem" at the levels they occur in the environment, there are some medications "for which some researchers have noted physiological effects in fish exposed to levels close to those occasionally reached in the environment. These include some ingredients used for contraception, hypertension and mood disorders."

The agency said how often this occurs and the possible environmental repercussions are unknown.

The study joins a small but growing body of research exploring the possible environmental impact of chemicals in pharmaceuticals, cosmetics and other products. Many of these chemicals are not removed by wastewater treatment plants, which were designed to remove bacteria and nutrients, experts said.

The topic is difficult to study partly because concentrations of chemicals in waterways can vary with season, hour and distance from treatment plants, and other medications in water may influence a chemical's effects.

The United States Geological Survey has found "intersex fish," or male fish that develop female sexual characteristics, in the Potomac River and its tributaries, raising questions about whether hormone residues might be responsible. A study in the journal Environmental Science and Technology found antidepressants like Prozac and Zoloft in the brains of fish collected downstream from wastewater discharge in Colorado and Iowa. But some antidepressants that were more common in those waterways, including Zyban and Citalopram, were not found as frequently in the fish.

In the Swedish study, researchers first tested perch in the wastewater-treated Fyris River, near the city of Uppsala, and found their muscle tissue contained six times the river's concentration of Oxazepam, said Tomas Brodin, the lead author and an assistant professor of ecology at Umea University.

Researchers then took baby fish hatched from the roe of wild perch in what they considered a drug-free waterway, and divided them into three groups of 25. One group had no exposure to Oxazepam; the other two were placed in water with what researchers called a low concentration, at three times higher than the River Fyris, or an extremely high concentration, at 1,500 times higher.

The more Oxazepam they ingested the more active the fish were, measured by the number of swimming motions in a 10-minute period. They were also less social, spending less time near a section of the tank with other fish and more time near an empty compartment. And they were quicker to grab and eat zooplankton. At the highest Oxazepam concentration, fish were also bolder, measured by how long it took them to leave a box in the tank and explore new territory.

"Basically, no one left the box before they were subjected to the drug," said Dr. Brodin, who said he saw the difference when he entered the room each day. The non-exposed fish "were hiding basically," while the others "were out there, greeting me. They were totally different fish."

In a statement, Matthew Bennett, senior vice president of the Pharmaceutical Research and Manufacturers of America, said the study yielded "somewhat expected results" because of its higher-than-natural concentrations. He said the behavioral changes were small, and the study methods contradicted "widely accepted protocols that determine how the low levels of Oxazepam found in the environment accumulate in fish. The environmental relevance and potential for long-term impact from this drug, which has been in use for decades are therefore debatable."

Joel A. Tickner, an environmental scientist at the University of Massachusetts, Lowell, who was not involved in the research, said he considered the study significant. "These effects may be very subtle," he said, but "what they're finding is it's biologically relevant."

Dr. Brodin, the lead author of the study, said the implications were unclear for perch, which might benefit from Oxazepam exposure by becoming more efficient eaters or be disadvantaged because enhanced risk-taking behavior might increase their vulnerability to predators. Zooplankton, algae and other organisms could also be affected by changes in fish behavior, he said.

Dr. Tillitt, the toxicologist with the Geological Survey, said, "We're smart enough and we should be able to design chemicals that fulfill these same sorts of functions but with less stress on the environment."